Академический Документы
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Amanda J. Tome
Table of Contents
Abstract ........................................................................................................................................... 4
Introduction ..................................................................................................................................... 5
Methods........................................................................................................................................... 6
Results ............................................................................................................................................. 9
Xanthophylls ..................................................................................................................... 22
Genetics............................................................................................................................. 24
Discussion ..................................................................................................................................... 25
Conclusion .................................................................................................................................... 29
References ..................................................................................................................................... 30
Appendix ....................................................................................................................................... 33
List of Tables
Table
2. Screening and Selection Tool for Identifying Studies Assessing the Relationship between
List of Figures
Figure
Abstract
Objective: To determine the effect of a diet rich in carotenoids in the prevention of age-related
Methods: Scholarly, English language studies, published between May 2010 and June 2017,
were identified via MEDLINE, CINAHL, and PubMed electronic databases. Randomized
control trials or observational studies investigating the effect of carotenoids from diet on the
development of AMD among adults were included. Included studies were critically evaluated
Results: Seven observational studies met the inclusion criteria and were included in this review.
All studies but one received a neutral rating. Of the five studies that investigated lutein and
zeaxanthin, three found a reduced risk of late or combined AMD among subjects with the highest
dietary intake and two only found a reduced risk among participants with genetic susceptibility.
Higher intake of lutein and zeaxanthin was associated with a reduced risk of early AMD among
CFH genotype carriers. All three studies that examined β-carotene found a reduced risk of late
or combined AMD. Only observational studies met the inclusion criteria, so a causal
Conclusion: A carotenoid-rich diet may be associated with a reduced risk of AMD, particularly
late AMD among a general adult population and early AMD among adult CFH genotype
carriers. More research and higher quality studies are needed to definitively establish this
Age-related macular degeneration (AMD) is the leading cause of blindness among adults
aged 50 years or older in the United States (U.S.) and is responsible for 8.7% of all blindness
cases globally (National Eye Institute [NEI], 2015; Wong et al., 2014). As AMD progresses, the
macula – the central region of the retina that regulates central vision – is damaged, resulting in
vision loss (NEI, 2015). Age-related macular degeneration is categorized into three stages: (1)
early AMD, which is characterized by the presence of a several soft, small (< 63 μm diameter)
drusen – small yellow lipid deposits that form beneath the retina, one medium (63 – 124 μm
diameter) druse, or mild pigment changes to the retinal pigment epithelium (RPE); (2)
intermediate AMD, which is characterized by the presence of a several medium drusen, one large
(> 124 μm diameter) druse, and/or RPE pigment changes; and (3) late AMD, which is
characterized by the presence of a large drusen, pigment RPE degradation, and vision loss
Hoskins Center for Quality Eye Care, 2015; NEI, 2015). In 2010, 9.1 million Americans had
early AMD and 2.1 million Americans had late AMD; however, the prevalence of early and late
AMD are projected to double by the year 2050, to 17.8 and 5.4 million Americans, respectively
(NEI, n.d.; Rein et al., 2009). In 2004, AMD was responsible for $575 million in direct medical
costs, which does not include lost productivity, home health care costs, and long-term care
The etiology for AMD is still mostly unknown; however, scientific evidence suggests
that age, race, and genetics are dominant, non-modifiable risk factors, and that oxidative stress
plays an important role in its pathogenesis (NEI, 2015; Shaw et al., 2016). Dietary antioxidants
CAROTENOID-RICH DIET AND AMD 6
are suspected to play a role in preventing or slowing the progression of AMD because
antioxidants neutralize free radicals created by oxidative stress and the macular pigment is
To date, there have been two systematic reviews investigating the role of dietary
supplements in AMD prevention and one systematic review, by Ma et al. (2011), investigating
the relationship between dietary lutein and zeaxanthin intake and AMD prevention. In their
review of studies published through April 2010, Ma et al. (2011), found that dietary lutein and
zeaxanthin did not significantly reduce the risk of early AMD but that dietary lutein and
zeaxanthin intake may prevent the risk of developing late AMD, and concluded that additional
research was needed for confirmation of their results. Therefore, the purpose of this review is to
systematically review and critically evaluate new scientific research to determine the effect of a
Methods
Search Strategy
Studies were identified by searching the electronic databases MEDLINE, CINAHL, and
PubMed, for studies published between May 1, 2010 and June 30, 2017, using various
permutations of the MeSH terms and keywords carotenoids, antioxidants, lutein, zeaxanthin,
and eye health. Searches were limited to scholarly, peer-reviewed journals and those available in
Table 1
Search Strategy
Keyword/MeSH Terms ‘AND’ keyword/MeSH Terms
Carotenoid AMD OR age-related macular degeneration
Carotenoid Eye health OR vision
Antioxidants AMD OR age-related macular degeneration
Antioxidants Eye health OR vision
Lutein OR zeaxanthin ARMD OR age-related maculopathy
Lutein OR zeaxanthin Eye health OR vision
To minimize bias, a screening and selection tool with defined inclusion and exclusion
criteria was created and is outlined in Table 2. Every title and abstract identified via the keyword
searches was screened using the predefined inclusion and exclusion criteria. National and
international randomized control trials, cohort, cross-sectional, and case-controlled studies that
included adults over the age of 18 years were included. In vitro, animal studies, and those
including children (< 18 years) were excluded. Only studies investigating diet as the
intervention and the diagnosis or presence of AMD as the primary outcome were included;
excluded. Full-text articles of all potentially relevant studies were obtained through the
electronic database if full-text was available or through West Chester University’s interlibrary
loan system, Iliad, and then reviewed for relevance using the screening and selection tool. All
studies that met the inclusion criteria were included in this review. References were exported
and organized using the bibliographic management software, RefWorks, and articles were
Table 2
Screening and Selection Tool for Identifying Studies Assessing the Relationship Between a Carotenoid-
Rich Diet and AMD Prevention
Include Exclude
Patient Population Adults (≥ 18 years) Children (<18 years)
Animals
Cells
Interventions Diet Pharmaceutical
AMD medical treatments/procedures
Dietary Supplements
Comparators No intervention/Placebo
Outcomes Diagnosis/presence of AMD Not diagnosis/presence of AMD
Study Design RCT, Cohort, Case-Controlled, Cross- Not an RCT, cohort, case-controlled, or
Sectional cross-sectional study
Language English Not English
Time May 2010 Before May 2010
Location U.S. and International
Pertinent reference information, the study design, the research objective, study population
characteristics, intervention details, results and primary outcomes, limitations, and authors’
conclusions were extracted from each study. In studies reporting multiple risk estimates, the risk
estimate that adjusted for the most confounding factors was extracted for this report.
Each included study was critically evaluated using the Quality Criteria Checklist for
primary research, which assigns a grade of positive, neutral, or negative, based on four relevance
and 10 validity questions (see Appendix A). A study is classified as (a) positive, if all of the
relevance and the majority of the validity questions and specific questions are answered
positively; (b) negative, if the majority of the validity questions are answered negatively; or (c)
CAROTENOID-RICH DIET AND AMD 9
neutral, if the majority of the validity questions are answered positively but at least one of the
Results
Literature Search
Using a combination of keyword searches, 1752 citations were identified via the
electronic databases (Figure 1). There were 766 duplicates identified and deleted, resulting in
986 titles and abstracts to be screened. The title and abstract screening process identified 70
potential citations for inclusion, and the full-text articles were obtained. Of those 70 citations, 63
were excluded because they did not meet the specified patient population, intervention, or
(n = 1752) (n = 0)
inappropriate
Studies included in intervention
qualitative synthesis inappropriate
(n = 7) outcome
Studies included in
Included
quantitative synthesis
(meta-analysis)
(n = 0)
CAROTENOID-RICH DIET AND AMD 11
Study Design
The extracted study characteristics are reported in Table 3, and the quality assessment
results are shown in Table 4. Of the seven studies included in this review, one was rated as
positive and the remaining six were rated as neutral. The study designs of the included studies
vary; however, all were observational study types, as none of the RCT studies met the inclusion
criteria. There were four cohort studies (Lin et al, 2017; Mares et al., 2011; Wang et al., 2014;
Wu, Cho, Willett, Sastry, & Schaumberg, 2015), two case-control studies (Aoki et al., 2016; Ho
et al., 2011), and one cross-sectional study (Nidhi, Mamatha, Padmaprabhu, Pallavi, &
Vallikannan, 2013). Of the four cohort studies, three were prospective studies (Lin et al., 2017;
Mares et al., 2011; Wu et al., 2015). Two studies solely focused on lutein and zeaxanthin (Lin et
al., 2017; Wu et al., 2015), whereas five studies investigated various dietary components,
including carotenoids (Aoki et al., 2016; Ho et al., 2011; Mares et al., 2011; Nidhi et al., 2013;
Wang et al., 2014). Three studies also investigated the role of diet and genetics on AMD (Ho et
al., 2011; Lin et al., 2017; Wang et al., 2014), although only two genotypes, CFH and ARMSS2,
were assessed in at least two studies. Four studies investigated the effect of diet on prevention of
early AMD (Ho et al., 2011; Lin et al., 2017; Mares et al., 2011; Wang et al., 2014), one on the
prevention of late AMD (Wu et al., 2015), and two on any stage of AMD (Aoki et al., 2016;
Table 3
Data Extraction Table of Studies Assessing the Relationship Between a Carotenoid-Rich Diet and AMD Prevention
Author/Year Purpose of Study Intervention Outcomes Conclusion Limitations
Study Population
Study
Design
Quality
Assessment
Rating
Lin et al., To assess the n = 10,295 Dietary No significant No suggested Assessed
2017 relationship Caucasian or xanthophyll differences in association prevalent not
between African (lutein & odds ratio (OR) between dietary incident
Study
dietary American zeaxanthin) for early AMD xanthophyll AMD
Design:
xanthophyll adults (80% intake measured and xanthophyll intake and early 6 year
Population-
intake and Caucasian, using a validated intake (Q1 = AMD among interval
based,
prevalent early 55% female, 66-item FFQ at 1.00, Q2 & Q3 = middle-aged between
prospective
AMD using 32.8% have 2 visit 1 (1987-89) 1.07, Q4 = 1.09, Caucasian and visits 1 & 3
cohort
data from the risk alleles), and visit 3 (1993- Q5 = 1.02, p = African Dietary
Rating: Ø Atherosclerosis aged 45-64 95) and adjusted .91) after American adults; xanthophyll
Risk in years (mean for estimated adjustments for however, more intake
Communities age 53.9±1 daily energy gender, age, research needed measured by
Study (ARIC) years), from intake smoking, caloric to explore effects FFQ
the United intake, and field of genetic Only 1 study
Prevalent AMD
States center susceptibility & group
(soft drusen
HDL metabolism Blinding
diameter ≥ 63 μm Greater
procedures
or loss of retinal xanthophyll
unclear
pigment intake
epithelium) significantly
determined via decreased odds
fundus of early AMD
photography at for Caucasian
CAROTENOID-RICH DIET AND AMD 13
Mountains Eye years, 38.2% FFQ OR for AMD both genetic and
Study (BMES) male, 54.5% administered by a and ≥ 1 serving environmental
and the non-smokers, trained dietitian fish/week among factors.
Rotterdam 40.9% 2 and analyzed adults with 0
Study (RS) genotype risk using the Dutch risk alleles (early
alleles Food 1.17; late 0.91)
Composition and 2 risk alleles
RS: n = 2778
Table (early 0.89; late
Control 0.54)
AMD assessed
Subjects: n =
using retinal OR for AMD
2006, mean
photography by and highest
age 65.01
trained specialists tertile of vitamin
years, 42.1%
during at least 1 C intake among
male, 33.0%
follow-up visit adults with 0
non-smokers,
(BMES follow- risk alleles (early
25.7% 2
ups every 5 0.91; late 0.78)
genotype risk
years; RS follow- and 2 risk alleles
alleles
ups 1997-99, (early 0.87; late
Case
2002-04, & 0.67)
Subjects: n =
2009-11)
772, mean
age 66.18
years, 40.8%
male, 32.7%
non-smokers,
43.6% 2
genotype risk
alleles
Nidhi et al., To explore n = 3549 Socio- AMD incidence Higher intake of 1/10 of
2013 AMD demographic, decreased as carotenoids, fundus
Urban
prevalence and lifestyle factors, lutein and specifically photographs
Study subjects: n =
putative risk and medical zeaxanthin lutein and were
Design: 2641, mean
CAROTENOID-RICH DIET AND AMD 17
Design: and zinc affect 56.7% female, vitamins A, C, intake of zinc susceptible adults analysis may
Nested case- incident early mean BMI and E, zinc, and (T1 HR = 2.25, may be reduced have skewed
control AMD among 26.5, 31.7% iron assessed, at T3 HR = 1.27, p by high dietary results
adults with non-smokers, baseline, via a = .03), β- intake of causing
Rating: Ø
genetic 44.6% non- self-administered carotene (T1 HR antioxidants, Ω-3 underestimati
susceptibility carriers of home checklist = 2.54, T3 HR = fatty acids, and on
by examining CFH Y402H (inquiring about 1.47, p = .05), zinc. Young Possible
adults with genotype, food and EPA/DHA (T1 adults with a confounding
early AMD 67.5% non- beverages HR = 1.97, T3 genetic risk of factors as
compared to carriers of consumed two or HR = 1.30, p = AMD should individuals
control LOC387715 more times per .03), and consume with a
subjects from a A69S month over the lutein/zeaxanthin sufficient healthy diet
prospective, geneotype preceding year, (T1 HR = 2.63, amounts of most likely
population- supplement use, T3 HR = 1.72, p antioxidants, also have
Case Subjects:
based cohort and dietary = .05) reduced zinc, and Ω-3 other
n = 517, mean
study, the habits/diets and a the risk of early fatty acids potentially
age 68.1 years,
Rotterdam 170-item FFQ AMD protective
56.5% female,
Study administered by a healthy
mean BMI Among
trained dietitian lifestyle
26.2, 32.0% LOC387715
and analyzed factors
non-smokers, genotype
using the Blinding
38.1% non- carriers, higher
electronic Dutch procedures
carriers of intake of zinc
Food unclear
CFH Y402H (T1 HR = 1.70,
Composition Intervention
genotype, T3 HR = 1.17, p
Tables not
58.9% non- = .03) and
sufficiently
carriers of Early AMD EPA/DHA (T1
described
LOC387715 (presence of a HR = 1.59, T3
Unclear if
A69S soft drusen or HR = 0.95, p =
participants
geneotype pigment .01) reduced the
are
abnormality) risk of early
assessed at AMD representativ
e of
baseline and 3
CAROTENOID-RICH DIET AND AMD 19
Table 4
Quality Assessment of Studies Assessing the Relationship Between a Carotenoid-Rich Diet and AMD Prevention
Author(s) Design Q1a Q2b Q3c Q4d Q5e Q6f Q7g Q8h Q9i Q10j QAk
Lin et al., 2017 Cohort Y N N/A N UC N Y Y Y Y Ø
Aoki et al., 2016 Case-Control Y Y Y N N UC Y Y Y N Ø
Wu et al., 2015 Cohort N Y N/A N N Y Y Y Y Y +
Wang et al., 2014 Cohort Y UC UC N UC Y Y Y Y Y Ø
Nidhi et al., 2013 Cross-Sectional Y Y N/A Y UC N Y Y Y Y Ø
Ho et al., 2011 Cohort Y UC Y N N N Y Y Y Y Ø
Mares et al., 2011 Cohort Y Y UC N N Y Y Y Y Y Ø
a
Q1=Question 1: Was the research question clearly stated?
b
Q2=Question 2: Was the selection of study subjects/patients free from bias?
c
Q3=Question 3: Were study groups comparable?
d
Q4=Question 4: Was method of handling withdrawals described?
e
Q5=Question 5: Was blinding used to prevent introduction of bias?
f
Q6=Question 6: Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were intervening factors
described?
g
Q7=Question 7: Were outcomes clearly defined and measurements valid and reliable?
h
Q8=Question 8: Was the statistical analysis appropriate for the study design and type of outcome indicators?
i
Q9=Question 9: Are conclusions supported by results with biases and limitations taken into consideration?
j
Q10=Question 10: Is bias due to study’s funding or sponsorship unlikely?
k
QA= quality assessment; l+=positive; m-=negative; nØ=neutral; oY=yes; pUC=unclear; qN/A=not applicable; rN=no
CAROTENOID-RICH DIET AND AMD 22
Xanthophylls
Lutein and zeaxanthin dietary intake was assessed in five of the seven included studies.
The amounts of xanthophylls reported in each study are described in Table 5. Three studies
found a reduced risk of AMD associated with higher dietary lutein and zeaxanthin intake (Nidhi
et al., 2013; Wang et al., 2014; Wu et al., 2015); two did not find an overall reduced risk except
among participants with a specific genetic risk (Ho et al., 2011; Lin et al., 2017). Higher dietary
consumption of lutein and zeaxanthin was found to reduce the risk of late AMD by 40% (RR =
0.59, p < .001; Wu et al., 2015), and early AMD among adults with 2 risk alleles of CFH and/or
ARMS2 genotype by 22% (OR = 0.78; Wang et al., 2014), and the risk of any form of AMD by
60% (OR = 0.38, p < .001; Nidhi et al., 2013). However, Lin et al. (2017) found no association
between the highest tertile dietary xanthophyll intake and early AMD among middle-aged adults
except among Caucasian carriers of one risk allele of CFH genotype (OR = 0.63, p = .28), and
Ho et al. (2011) only found a reduced risk of early AMD among carriers of CFH genotype who
consumed the highest tertile of lutein and zeaxanthin (T1 HR = 2.63, T3 HR = 1.72, p = .05).
CAROTENOID-RICH DIET AND AMD 23
Table 5
Other Carotenoids
Three studies investigated the effect of other specific carotenoids (Aoki et al., 2016;
Nidhi et al., 2013; Wu et al., 2015), and one study investigated the effect of a healthy diet, which
is rich in fruit and vegetables and, as such, rich in carotenoids (Mares et al., 2011). Beta-
carotene was assessed in all three studies and was found to reduce the risk of AMD in all studies
to varying degrees. The amounts of β-carotene reported in each study are described in Table 6.
Higher dietary intake of β-carotene was found to reduce the risk of AMD by Aoki et al. (2016;
OR = 0.2, p < .001), Wu et al. (2015; RR = 0.82, p = .03), and by Nidhi et al. (2013; OR = 0.38,
p < .001). In addition to β-carotene, Wu et al. (2015) also investigated α-carotene and β-
cryptoxanthin and found that higher intakes of both reduced the risk of late AMD (RR = 0.69, p
< .001 and RR = 0.73, p = .002 respectively) but did not find a reduced risk for intermediate
CAROTENOID-RICH DIET AND AMD 24
AMD. Mares et al. (2011) found that the healthiest diets based on the 2005 modified Healthy
Eating Index (70-80 points) had a reduced risk of AMD (OR = 0.54, p = .01).
Table 6
Genetics
Three of the seven included studies investigated the role of diet and genetic susceptibility
on AMD prevention (Ho et al., 2011; Lin et al., 2017; Wang et al., 2014). As previously
discussed, higher dietary intake of lutein and zeaxanthin is associated with a reduced risk of
AMD among carriers with the CFH genotype but not among carriers of LOC387715 genotype
(Ho et al., 2011; Lin et al., 2017; Wang et al., 2014). Inconclusive evidence exists to determine
whether xanthophyll intake reduces the risk of AMD among carriers of ARMS2 genotype.
Wang et al. (2014) found that lutein and zeaxanthin reduced the risk of early AMD by 22%
among adults with a high genetic risk, i.e., carriers of two alleles of the CFH and/or ARMS2
genotype, but Lin et al. (2017) did not find a reduced risk among adults with ARMS2 genotype.
In addition to finding a reduced risk of AMD among CFH genotype carriers with higher
xanthophyll intakes, Ho et al. (2011) also found a reduced risk of early AMD among carriers of
CAROTENOID-RICH DIET AND AMD 25
the CFH genotype who had higher intake of β-carotene (M = 2.36 mg/day; T1 HR = 2.54, T3 HR
= 1.47, p = .05) but did not find a reduced risk of early AMD among carriers of LOC387715
genotype.
Discussion
preventing AMD. After applying the inclusion criteria to the substantial number of search
results, only seven studies were included in this review. This number was smaller than
anticipated, considering that dietary antioxidants are suspected to play a role in AMD
pathogenesis, and the previous systematic review by Ma et al. (2011) recommended further
research; however, current research appears to be focusing on the effects of dietary supplements
on AMD pathogenesis. Notwithstanding the small number of included studies, piloting the
search keywords and searching three comprehensive electronic health databases provide
The included studies reported carotenoid intake in different manners, which make it
difficult to analyze and compare the amount of each nutrient. Six of the studies reported
amounts as micrograms or milligrams per day (Aoki et al., 2016; Ho et al., 2011; Mares et al.,
2011; Nidhi et al., 2013; Wang et al., 2014; Wu et al., 2015); whereas Lin et al. (2017) reported
nutrient intake as micrograms per 1,000 kcal, and Wang et al. (2014), and Wu et al. (2015)
reported carotenoid amounts by population group even though the hazard risks were calculated
using pooled data. Lastly, Nidhi et al. (2013) did not report the amount of xanthophylls that was
The studies investigating the effect of dietary lutein and zeaxanthin on preventing AMD
have produced mixed results, although all five of the studies reported a decreased risk of AMD
CAROTENOID-RICH DIET AND AMD 26
among at least one group or sub-group who consumed the highest tertile or quintile. The highest
tertile/quintile means range from 1.43 to 5.47 mg/day (Ho et al., 2011; Wang et al., 2014; Wu et
al., 2015) and the reported ranges range from 1.01 to 32.65 mg/day (Lin et al., 2017; Nidhi et al.,
2011). Two studies investigated the general population (Nidhi et al., 2013; Wu et al., 2015), and
the other three studies investigated a genetically susceptible population (Ho et al., 2011; Lin et
al., 2017; Wang et al., 2014). The twenty-year prospective cohort study, by Wu et al. (2015),
found a 40% reduced risk of late AMD among participants with the highest xanthophyll intake
but did not find an association with intermediate AMD, which is consistent with the findings of
the systematic review by Ma et al. (2012). Nidhi et al. (2013) found a 60% reduced risk of
AMD, but the researchers combined early and late stages when calculating the risk hazard due to
the small percentage of AMD cases, which prevents distinguishing how xanthophylls affect early
and late AMD and may reduce the power of the results.
All three studies that investigated the effect of dietary lutein and zeaxanthin intake and
genetic susceptibility on early AMD found a reduced risk among CFH genotype carriers (Ho et
al., 2011; Lin et al., 2017; Wang et al., 2014). Wang et al. (2014) found a 20% reduced risk of
early AMD among participants with at least 2 risk alleles of CFH or ARMS2 genotypes and the
highest dietary lutein and zeaxanthin intake. Ho et al. (2011) found a reduced risk among CFH
genotype carriers but not among LOC387715 genotype carriers, and Lin et al. (2017) only found
a reduced risk among Caucasian participants with one CFH genotype risk allele (moderate risk)
but not among African American participants, participants with ARMSS2 genotype carriers, or
Caucasian participants with 2 CFH genotype risk alleles. These results are inconsistent with the
Ma et al. (2012) review, which did not find an association between dietary lutein and zeaxanthin
and early AMD prevention; however, included studies of that review did not investigate the role
CAROTENOID-RICH DIET AND AMD 27
of genetics. Because Wang et al. (2014) combined two genotypes, it is difficult to determine if
the results were driven by one particular genotype. It is unclear why Lin et al. (2017) found a
statistically significant risk reduction among moderate risk Caucasian CFH genotype carriers and
not among high genetic risk (2 risk alleles), but it is possible that the substantially smaller
number of high genetic risk participants reduced the statistical power of their results. The ethnic
differences found by Lin et al. (2017) are difficult to compare, as that study was the only one to
was substantially limited in the other two studies investigating genetics (Ho et al., 2011; Wang et
al., 2014). Ho et al. (2011) was the only study to investigate the LOC387715 genotype, so it is
Higher dietary intake of β-carotene was found to reduce the risk of late or combined
AMD in all three studies that investigated it (Aoki et al., 2016; Nidhi et al., 2013; Wu et al.,
2015). The highest tertile/quintile means range from 6.04 to 8.15 mg/day (Aoki et al., Wu et al.,
2015). Wu et al. (2015) found a reduced risk only for late AMD and not intermediate AMD;
Aoki et al. (2016) only investigated late AMD; and Nidhi et al. (2013) combined early and late
AMD cases in their statistical analysis. These results are not surprising, since Ma et al. (2012)
found that high dietary intake of lutein and zeaxanthin intake prevented only late AMD and not
early AMD. Although β-carotene is a different carotenoid than lutein and zeaxanthin, all three
are common nutrients in fruit and vegetables, and it is difficult to isolate the effect of a single
nutrient when investigating diet. Wu et al. (2015), which found that α-carotene and β-
cryptoxanthin also reduced the risk of late AMD, was the only study to investigate other
carotenoids; however, Mares et al. (2011) investigated a healthy, and presumably carotenoid-
rich, diet and found a reduced risk of early AMD. Mares et al. (2011) is the only study that
CAROTENOID-RICH DIET AND AMD 28
found a reduced risk of early AMD among a general, non-genetically susceptible population,
which may be due to the poor generalizability of its sample population, as participants were
The present review has a few strengths. First, all of the included studies adjusted for
confounding variables, including, age and smoking status. Second, a majority of the studies
included a large sample population and the cohort studies were of long duration.
The present review has several limitations. First, this review, including the screening and
selection process, was prepared by a single, independent researcher instead of the standard two
independent researchers, which creates a possibility for bias and erroneous application of the
inclusion criteria. It was impossible for two researchers to apply the inclusion criteria, as this
However, application of the inclusion criteria was thoroughly discussed with the present
researcher’s academic advisor in an attempt to minimize errors and bias. Second, the present
review may be subject to publication bias, though this risk appears to be minimal, since the
review includes both positive and negative results, the results are consistent with the prior
systematic review (Ma et al., 2012), and all reviews are subject to the same publication bias. The
present review was limited to studies published in the English language, as the present researcher
can read only English, and there was insufficient time to translate any non-English articles.
Lastly, the included studies are all observational protocols, which may be subject to confounding
effects and are not of sufficiently high quality to ascertain a causal relationship; however, this
Age-related macular degeneration is the leading cause of blindness in the U.S. among the
elderly and, as such, is a public health concern (NEI, 2015). The present review detected an
indication that dietary carotenoids may reduce the risk of late AMD among the general
population and may reduce the risk of early AMD among Caucasian CFH carriers, but more
research is warranted to investigate these relationships. Higher quality studies are recommended
to examine the relationship between dietary carotenoid consumption and the prevention of late
AMD and to investigate the relationship between genetic susceptibility, dietary carotenoids, and
early AMD prevention. Despite the need for more research, it is not unwarranted to recommend
to the public a healthy, carotenoid-rich diet, as this recommendation aligns with the current
dietary guidelines for Americans (U.S. Department of Health and Human Services & U.S.
Conclusion
A diet rich in carotenoids may be associated with a reduced risk of AMD, particularly
late AMD among a general adult population and early AMD among adult carriers of the CFH
genotype. More research and higher quality studies are needed to definitively establish this
association and to ascertain the amount of carotenoids needed to prevent AMD. The strength of
the studies mostly rated between fair and limited, thus earning it an overall grade of limited (see
Appendix B).
Grade: III
CAROTENOID-RICH DIET AND AMD 30
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CAROTENOID-RICH DIET AND AMD 33
Appendix A
Appendix B
Conclusion Grading Table of Studies Assessing the Relationship Between a Carotenoid-Rich Diet and Preventing Age-Related
Macular Degeneration (AMD)
Strength of Grades
Evidence I II III IV V
Elements
Good Fair Limited Expert Opinion Only Grade Not
Assignable
Quality Studies of strong design Studies of strong Studies of weak design No studies available No evidence
for question design for question for answering the that pertains to
Scientific question Conclusion based on question being
rigor/validity Free from design flaws, with minor usual practice, expert addressed
bias and execution methodological OR consensus, clinical
Considers design problems concerns, OR experience, opinion, or
and execution Inconclusive findings extrapolation from basic
Only studies of due to design flaws, research
weaker study bias or execution
design for question problems
Consistency Findings generally Inconsistency Unexplained Conclusion supported NA
consistent in direction among results of inconsistency among solely by statements of
Of findings and size of effect or studies with strong results from different informed nutrition or
across studies degree of association, and design, OR studies OR single medical commentators
statistical significance study unconfirmed by
with minor exceptions at Consistency with other studies
most minor exceptions
across studies of
weaker design
CAROTENOID-RICH DIET AND AMD 37
Quantity One to several good Several studies by Limited number of Unsubstantiated by Relevant
quality studies independent studies published research studies have
Number of investigators studies not been done
studies Large number of subjects Low number of
studied Doubts about subjects studied and/or
Number of adequacy of sample
subjects in Studies with negative size to avoid Type I inadequate sample size
studies results have sufficiently and Type II error within studies
large sample size for
adequate statistical power
Clinical Impact Studied outcome relates Some doubt about Studied outcome is an Objective data Indicates area
directly to the question the statistical or intermediate outcome unavailable for future
Importance of clinical significance or surrogate for the research
studied outcomes Size of effect is clinically of the effect true outcome of
meaningful interest
Magnitude of
effect Significant (statistical) OR
difference is large
Size of effect is small
or lacks statistical
and/or clinical
significance
Generalizability Studied population, Minor doubts about Serious doubts about Generalizability limited NA
To population of intervention and generalizability generalizability due to to scope of experience
interest outcomes are free from
serious doubts about narrow or different
generalizability study population,
intervention or
outcomes studied